A Transcriptomic Meta-Analysis Identifies Differentially Expressed Genes across Different Types of Cancer and Their Association with Checkpoint Inhibitor Immunotherapy

Abstract

Background Checkpoint inhibitor, anti-Programmed cell death protein1/Ligand (PD1 / PDL1) immunotherapy achieved great success in modulating the immune system to reinvigorate targeted immune fight against several types of cancer. However, patients’ clinical response to this cancer immunotherapy varies widely. Biomarkers that can predict the greatest response to the anti-PD1 immunotherapy could help to personalize the maximum benefit for the right patient.Results This study explored transcriptomic biomarkers that were associated with the response (or no-response) to the anti-PD1/PDL1 immunotherapy in seven types of cancer [Malignant Pleural Mesothelioma (n=8), Head and Neck cancer (n=3), Lung Non-Squamous cancer (n=15), Squamous Lung cancer (n=8), Melanoma (n=23), Melanoma Skin Metastasis (n=10), and Renal Cell Carcinoma (n=11)]. The most common differentially expressed genes (105 genes) were between melanoma skin metastasis and renal cell carcinoma; followed by malignant pleural mesothelioma and renal cell carcinoma, which had 79 common differentially expressed genes; then malignant pleural mesothelioma and melanoma skin metastasis, which had 46 differentially expressed genes in common. Many similar (parallel) and dissimilar (anti-parallel) gene expression signatures were identified in this study. Parallel signature Differentially Expressed Genes (DEGs) are genes up-regulated together in either response or no-response group of different types of cancer, while the anti-parallel DEGs show up-regulation in the response group of one type of cancer while same genes are up-regulated in the no-response group of another different type of cancers. Target of Myb1 like 1 Membrane Trafficking Protein gene (TOM1L1) was found to be common among malignant pleural mesothelioma, melanoma skin metastasis, and renal cell carcinoma and was up-regulated in the cancer patients’ samples that did not respond to the anti-PD1/PDL1 immunotherapy. This study also found that differentially expressed Plasminogen Activator, Urokinase Receptor gene (PLAUR), was common among squamous lung cancer, melanoma and melanoma skin metastasis, and was up-regulated in the patients’ samples that responded to the anti-PD1/PDL1 immunotherapy.Conclusion In summary, this study identified DEGs biomarkers that can predict the response or no-response to the anti-PD1 immunotherapy across seven types of cancer. It also affirms the attention to important genes like TOM1L1 and PLAUR for their potential function in the cancer dissemination and metastasis.